Diabetes mellitus is a chronic disease which, in addition to other well known complications, has deleterious effects on the progress and outcome of pregnancy. It results in offspring who are more likely to be congenitally malformed, macrosomic, premature, or stillborn. Mothers with diabetes during pregnancy are more likely to have toxemia, cesarean sections, and also have higher mortality. The effects on the offspring of women who have diabetes during pregnancy are long lasting, possibly for life. In addition, diabetes can first occur during pregnancy or can occur only during pregnancy (gestational diabetes). The purpose of the project is to determine the effects of diabetes mellitus and pre-diabetes on the complications and outcome of pregnancy in women in the Gila River Indian Community and on the subsequent growth and development of their children. We hope to gain a better basis for understanding mechanisms by which the diabetic pregnancy affects the offspring. The diabetes status of every woman is determined at two-yearly intervals and during the third trimester of each pregnancy. The characteristics of women who have diabetes during the pregnancy (diabetics) are compared to those of women who are normal during the pregnancy and subsequently develop diabetes (pre-diabetics) or remain normal (non-diabetics). The outcome of these pregnancies is assessed by review of both mother's and infant's hospital records. The offspring of these pregnancies are followed at two-yearly intervals after the age of 5 years. These biennial examinations include measurement of numerous parameters including glucose tolerance, height, and weight. An attempt is also made to determine the diabetes status of the fathers of these offspring so that familial and genetic factors can be evaluated as well as the effects of the intrauterine environment. Results to date indicate that the diabetic intrauterine environment has effects on the development of diabetes and obesity in the offspring which are greater than can be attributed to genetic factors alone.